Tumor rejection is dependent on the production of a population of sensitized thymus derived lymphocytes or T lymphocytes. Precursor T cells arising from the bone marrow or spleen migrate to the thymus where they differentiate under the influence of thymic factors. This differentiation and the possible functional roles of T cell antigens in cellular communication are of primary importance in the immunology of oncogenesis. Thymus dependent differentiation of marrow stem cells is accompanied by the rapid appearance of T cell specific antigens. In the mouse these are: theta antigen (theta) (also called Thy-1), brain-associated theta (BA theta), thymus leukemia and Ly antigens. Theta and BA theta antigens are proposed to be gangliosides and the carbohydrate structure of these glycosphingolipids will be determined. Evidence is presented that the BA theta antigen is covered or obscured in bone marrow stem cells and the thymus differentiating agent causes a rapid exposure to cytolytic anti-BA theta antisera. The expression of theta and BA theta and the mechanism of cell surface exposure under the influence of thymic factor will be studied using the following membrane probes: 1) lactoperoxidase catalyzed radioiodination followed by separation of membrane proteins by sodium dodecyl-sulfate--polyacrylamide gel electrophoresis; 2) galactose oxidase treatment followed by sodium borotritide-reduction, analysis of membrane proteins as in 1, and of radioactive membrane glycolipids by thin layer chromatography; 3) specific antibody cytolysis to measure degree of antigen exposure; 4) cholera toxin, which binds to cell surface monosialoganglioside (theta), will be used to study the mechanism of adenylate cyclase stimulation in lymphocytes. Membrane changes which occur during thymic factor differentiation will also be studied by isolation of plasma membranes of marrow stem cells, thymic factor-treated marrow cells, and thymocytes. Differentiation changes will be determined by electrophoresis of membrane proteins in sodium dodecylsulfate. BIBLIOGRAPHIC REFERENCES: Miller, H. C. and W.J. Esselman. 1975. Modulation of the immune response by antigen-reactive lymphocytes after cultivation with gangliosides. J. Immuno. 115, 839-843.